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Solid Lipid Nanoparticles SLNs for Intracellular Targeting Applications
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Lung targeted liposomes for treating ARDS.

Sivan Arber Raviv1, Mohammed Alyan2, Egor Egorov1

  • 1The Louis Family Laboratory for Targeted Drug Delivery and Personalized Medicine Technologies, Department of Chemical Engineering, Technion - Israel Institute of Technology, Haifa 32000, Israel.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|March 31, 2022
PubMed
Summary
This summary is machine-generated.

We developed liposomes for Acute Respiratory Distress Syndrome (ARDS) treatment, co-loading methylprednisolone and N-acetyl cysteine. Combined intravenous and endotracheal delivery showed superior therapeutic effects in reducing lung inflammation and mucus.

Keywords:
ARDSCOPDCovid-19LiposomeLung inflammationMucusNanotechnologyPulmonary

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Pulmonary Medicine

Background:

  • Acute Respiratory Distress Syndrome (ARDS) presents high mortality rates due to diffuse lung damage and impaired gas exchange.
  • Current treatments for ARDS often have limitations in effectively targeting lung inflammation and mucus buildup.

Purpose of the Study:

  • To develop and assess 100-nm liposomes for pulmonary delivery to treat ARDS.
  • To optimize liposomal composition for mimicking lung surfactant and co-load methylprednisolone (MPS) and N-acetyl cysteine (NAC).

Main Methods:

  • Liposomes were formulated with DPPC, co-loading MPS (98% efficiency) and NAC (92% efficiency).
  • In vitro studies used LPS-stimulated macrophages to assess anti-inflammatory effects and mucus penetration.
  • In vivo studies in mice utilized an LPS-induced lung inflammation model, comparing intravenous (IV) and endotracheal (ET) nanoparticle administration.

Main Results:

  • Liposomes demonstrated reduced TNFα and nitric oxide (NO) secretion in vitro.
  • NAC enhanced nanoparticle penetration through mucus in vitro.
  • Both IV and ET liposome administration led to significant accumulation in inflamed lungs over 48 hours.
  • Nanoparticle treatment showed superior therapeutic effects compared to free drugs, with combined IV/ET delivery yielding the best outcome in reducing lung inflammation and cytokine secretion (TNFα, IL-6, IL-1β).
  • The DPPC lipid component alone also exhibited a therapeutic role in reducing lung inflammation.

Conclusions:

  • Optimized liposomes effectively deliver MPS and NAC to inflamed lungs, showing significant therapeutic potential for ARDS.
  • Comparing IV and ET delivery, combined administration provides the most effective treatment by reaching both lung endothelial and epithelial cells.
  • Liposomes represent a promising platform for treating lung diseases, with potential for further development in pulmonary drug delivery.